Release of lipoprotein lipase from Ehrlich ascites tumor produced by an association with a rapid increase in cyclic AMP content.
Although it is considered that the lipoprotein metabolism in tumor plays an important role in growth and multiplication, it is not clear as to the details. Lipoprotein lipase (LPL) is a key enzyme responsible for the hydrolysis of lipoprotein-triacylglyceride. In this study, we examined the regulatory step of LPL in lipoprotein metabolism of Ehrlich ascites tumor and especially the enzyme-release from the tumor cells. When LPL was stimulated to release from the tumor cells by the low molecular weight dextran sulfate (3.2 kDa), cyclic AMP content in the tumor cells was observed to increase rapidly in a time-dependent manner up to 30 s; its maximal effect was 1.5-fold higher than the basal level of cyclic AMP. The increase in cyclic AMP content was more enhanced in the presence of isobutylmethylxanthine and was never suppressed by propranolol. Moreover, cyclic AMP-dependent protein kinase (PKA) activity in the tumor cells was also recognized to elevate in a time- and dose-dependent manner. In addition, the release of LPL activity from the tumor cells was inhibited by 2',5'-dideoxyadenosine. These results suggest that LPL in the tumor cells is released through a pathway involving an activation of PKA associated with the rapid increase in cyclic AMP content.
Morita
T
T
Second Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Japan.
Ueki
H
H
Kanagawa
A
A
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D051379:Mice; D011433:Propranolol / Q000494:pharmacology
D016264:Dextran Sulfate; D011433:Propranolol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D008071:Lipoprotein Lipase; D015056:1-Methyl-3-isobutylxanthine